Prospective validation of risk prediction indexes for acute and delayed chemotherapy-induced nausea and vomiting.

BACKGROUND: Despite the use of standardized anti-emetic guidelines, up to 20% of cancer patients suffer from moderate-to-severe chemotherapy-induced nausea and vomiting (cinv)-that is, grade 2 or greater according to the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. We previously developed cycle-based prediction models and associated scoring systems for acute and delayed cinv. As part of the validation process, we prospectively evaluated the ability of the scoring systems to accurately identify patients deemed to be high risk for grade 2 or greater cinv. METHODS: Patients who were receiving any chemotherapy for solid tumours and who consented to participate were provided with symptom diaries. Compliance to the diaries was enhanced by 24-hour and 5-day telephone callbacks after chemotherapy in every cycle. All patients received anti-emetic prophylaxis as prescribed by the treating physician. Before each cycle of chemotherapy, the acute and delayed cinv scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression modelling was then applied to compare the risk for grade 2 or greater cinv between patients considered to be at high and at low risk. The external validity of each system was also assessed using an area under the receiver operating characteristic curve (auroc) analysis. RESULTS: We collected cinv outcomes data from 95 patients during 181 cycles of chemotherapy. The incidence of grade 2 or greater acute and delayed cinv was 17.7% and 18.2% respectively. As previously identified, major predictors for grade 2 or greater cinv included younger patient age, platinum- or anthracycline-based chemotherapy, low alcohol consumption, earlier cycles of chemotherapy, previous history of morning sickness, and prior emetic episodes after chemotherapy. The acute and delayed scoring systems both had good predictive accuracy when applied to the external validation sample (acute-auroc: 0.69; 95% confidence interval: 0.59 to 0.79; delayed-auroc: 0.70; 95% confidence interval: 0.60 to 0.80). Patients identified by the scoring systems to be at high risk were 2.8 (p = 0.025) and 3.1 (p = 0.001) times more likely to develop grade 2 or greater acute and delayed cinv. CONCLUSIONS: The present study demonstrates that our scoring systems are able to accurately identify patients at high risk for acute and delayed cinv. Application and planned continued refinement of the scoring systems will be an important means of patient-specific risk assessment that will allow for optimization of anti-emetic therapy.

Cognitive structure of executive deficits in patients with frontal lesions performing activities of daily living.

OBJECTIVE: Executive function in activities of daily living (ADL) were investigated in 10 patients with excised frontal lobe tumours. METHOD: The patients with frontal lesions were compared to 10 normal controls with a neuropsychological test battery, a script generation task and a realistic implementation of complex multi-task ADL (planning and preparing a meal). RESULTS: The patients manifested numerous basic executive deficits on the paper-pencil tests, were unimpaired on the script generation task despite an aberrant semantic structure and manifested marked anomalies in the meal preparation task. CONCLUSION: Frontal lobe deficits in lengthy complex multi-task ADL can be explained by impairment of several executive functions, generalized slowness of performance and paucity of behaviour.

Strategic sequence planning and prospective memory impairments in frontally lesioned head trauma patients performing activities of daily living.

The aim of this research was to study strategic sequence planning and prospective memory in activities of daily living (ADL) in 10 patients with frontal lobe lesions after a mild to moderate closed head injury (CHI). The lesions were documented radiologically. The CHI patients were compared to 12 normal controls with a neuropsychological test battery and a realistic simulation of complex multitask ADL (planning and preparing a meal). Though the CHI patients were significantly slow on one test and subject to interference on an attention test, they manifested no basic executive or memory deficit on the paper-pencil tests. However, the CHI patients manifested marked anomalies in the organization of behavior in the meal preparation task. While small sequences of actions were easily produced, large action sets could not be correctly executed. An outstanding difficulty in strategic planning and prospective memory, particularly time-based more than event-based, appears to be an important underpinning of the impairment of ADL observed in the CHI patients with frontal lobe lesions.

Behavioral disorganization in schizophrenia during a daily activity: the kitchen behavioral scoring scale.

Executive dysfunction has been extensively described in schizophrenia and has been found to correlate with the negative symptoms of the disease. However, executive dysfunction is usually assessed by cognitive tests, and these are not necessarily good predictors of an individual's daily functioning. This study aimed to discover whether executive dysfunction in schizophrenia can be measured by analyzing a daily routine such as cooking a meal. Behavior was scored on the basis of the optimal sequence of macrostructures (order of dishes) and microsteps (order of actions) that must be performed to prepare the meal in a minimum of time and with the smallest delay between the completion of the first and last dishes. The results showed that patients with schizophrenia make macrostructure but not micro-step sequencing errors. The number of repetitions and omissions and the delay between the completion of the first and last dish were all greater in patients than in control subjects. In patients with schizophrenia, but not in normal controls, these behavioral malfunctions were significantly correlated with both negative symptoms and performance on the executive tasks. Poor performance on the memory tests was not correlated with the behavioral malfunction. Therefore, daily functioning in schizophrenia may be specifically influenced by executive dysfunction in schizophrenia, and this can be quantitatively assessed with a behavioral scale of action sequences.

Defective representation of knowledge in Parkinson's disease: evidence from a script-production task.

The deficits seen in frontal-lobe patients and in the elderly show clearly that spontaneous script generation depends on good frontal-lobe function. Shallice, however, has proposed that one aspect of script generation (contention scheduling, CS) which is involved in the activation and maintenance of overlearned or routine scripts may depend more on the basal ganglia. Patients with Parkinson's disease would thus be expected to manifest deficits somewhat different from those observed in frontal-lobe patients when generating scripts. The performances of 16 nondemented and nondepressed patients with idiopathic Parkinson's disease were compared to those of 16 age-matched normal control subjects under two experimental conditions; routine, forward script generation and nonroutine, backward script generation. Parkinsonian patients generated scripts significantly deprived of contextual elements in the forward condition and made significantly more sequencing and perseverative errors in both forward and backward conditions than did normal subjects. They also produced a significantly higher number of irrelevant intrusions, in both conditions, than did controls. These results support, in a general sense, Shallice's notion that the basal ganglia are important in script generation; however, other specific predictions of Shallice's model were not supported by our findings.

The scripting of activities of daily living in normal aging: anticipation and shifting deficits with preservation of sequencing.

The purpose of this study was to elaborate upon Shallice's frontal lobe model by evaluating 20 elderly normal and 20 young adult controls, all women, with cognitive tests, a paper-pencil script generation task and a kitchenette meal preparation task. The elderly were significantly weaker on standardized tests of executive functions and on the paper-pencil script generation task. An anticipation and a sequencing impairment clearly emerged. Though anticipation and shifting were compromised in the kitchenette script task, sequencing was however preserved. This supports Shallice's notion according to which scripting is hierarchically organized with top level components being more frontal lobe dependent (supervisory attentional system or SAS) and the lower level components more tributary to subcortical circuits involving procedural learning (contention scheduling or CS).

Mental representation of knowledge following frontal-lobe or postrolandic lesions.

The aims of this study were to examine the role of the prefrontal cortex in the representation of familiar activities using scripts, and to compare both Shallice's [Phil. Trans. Roy. Soc. Lond. B. Vol. 298, pp. 199-209, 1982] and Grafman's [Integrating Theory and Practice in Clinical Neuropsychology, pp. 93-138, Lawrence Erlbaum, Hillsdale, New Jersey, 1989] models of schematic representation of knowledge. Twelve patients with frontal-lobe damage, nine with postrolandic lesions, and 13 normal control subjects were asked to generate actions belonging to six different scripts in a forward condition, and to two others in a backward condition. The latter condition was included to test Shallice's hypothesis that damage to the frontal lobes would only affect the execution of non-routine tasks. The results showed that patients with frontal-lobe lesions produced scripts that were deprived of contextual elements and made more sequencing errors in the forward condition than matched normal control subjects, hence suggesting that the frontal cortex contributes to the production of an adequate mental representation of routine events. By contrast, the performance of the two clinical groups did not differ from the control subjects in their ability to generate scripts in the backward condition, although these three groups of subjects generated fewer actions in the latter condition. Further qualitative analyses demonstrated that patients with parietal-, but not with temporal-lobe lesions, produced sequencing errors in both forward and backward conditions. The latter findings suggest that the frontal lobes, together with the parietal cortex, may play a special role in establishing the spatio-temporal position of events within a script. The results of this study are discussed in terms of the recent models developed by Shallice and Grafman concerning the contribution of the frontal lobes in the mental representation of knowledge.

A peer review quality assurance program in drug information.

The development and implementation of a peer review quality assurance program for a drug information service is described. Eight drug information centres across Canada initially agreed to participate as peer reviewers. Critera were developed to select drug information requests that would qualify for the program. Peer review responses were compared to the centre's response by a panel of four drug information pharmacists. Thirteen of 14 requests sent to peer reviewers were returned and there was agreement between the conclusions and recommendations provided in the responses by our drug information centre and the peer review pharmacist in 11 cases. Peer reviewer pharmacists tended to prepare more in depth responses. This represents the first report of a peer review quality assurance program for a drug information service.